Bone Material Elasticity in a Murine Model of Osteogenesis Imperfecta

Mehta, Shreefal S.; Antich, Peter P.; Landis, William J.

doi:10.3109/03008209909005282

Cited by 19 publications

(13 citation statements)

References 54 publications

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“…less plastic deformation) in the oim bone matrix compared to wild type mice. Our local nanoindentation results are comparable to the findings of Mehta et al who also measured a decrease in elastic modulus in oim using ultrasound critical-angle reflectometry [19] . It should be noted that it was necessary to dehydrate and fully infiltrate our samples with PMMA for qBSEM analysis.…”

Section: Discussionsupporting

confidence: 90%

Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice

Vanleene

Porter

Guillot

et al. 2012

Bone

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Bone is a complex material with a hierarchical multi-scale organization from the molecule to the organ scale. The genetic bone disease, osteogenesis imperfecta, is primarily caused by mutations in the collagen type I genes, resulting in bone fragility. Because the basis of the disease is molecular with ramifications at the whole bone level, it provides a platform for investigating the relationship between structure, composition, and mechanics throughout the hierarchy. Prior studies have individually shown that OI leads to: 1. increased bone mineralization, 2. decreased elastic modulus, and 3. smaller apatite crystal size. However, these have not been studied together and the mechanism for how mineral structure influences tissue mechanics has not been identified. This lack of understanding inhibits the development of more accurate models and therapies. To address this research gap, we used a mouse model of the disease (oim) to measure these outcomes together in order to propose an underlying mechanism for the changes in properties. Our main finding was that despite increased mineralization, oim bones have lower stiffness that may result from the poorly organized mineral matrix with significantly smaller, highly packed and disoriented apatite crystals. Using a composite framework, we interpret the lower oim bone matrix elasticity observed as the result of a change in the aspect ratio of apatite crystals and a disruption of the crystal connectivity.

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Section: Discussionsupporting

confidence: 90%

Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice

Vanleene

Porter

Guillot

et al. 2012

Bone

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“…Degree of mineralization and collagen arrangement also are reported to correlate to the clinical classification [9][10][11][12]. In the studies of mechanical testing of OI mice models, the mechanical properties are suggested to correlate with the clinical types in whole bone structural level [15][16][17][18][19][20][21]. However, there is scant information regarding the relationship between intrinsic mechanical properties and the clinical classification.…”

Section: Discussionmentioning

confidence: 97%

“…There are several studies investigating the mechanical properties of OI bone tissue. Most of the mechanical property studies used animal models (mainly murine) at whole bone structural level [15][16][17][18][19][20][21]. These studies indicate that the mechanical properties are decreased in OI bone.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Nanoindentation Measurements Between Osteogenesis Imperfecta Type III and Type IV and Between Different Anatomic Locations (Femur/Tibia versus Iliac Crest)

Fan

Smith

Harris

et al. 2007

Connective Tissue Research

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Nanoindentation was used to compare the intrinsic mechanical properties of bone tissue (iliac crest biopsy) from children with type III and type IV osteogenesis imperfecta (OI). Young's modulus and hardness values were not significantly different between the two clinical severity groups on either cortical or trabecular measurement. In comparing the ratio of modulus over hardness (E/H) between OI type III and IV. The type III bone showed a marginally significant decrease for cortical bone and significant decrease for trabecular bone, which indicated that the OI type III bone was more brittle than OI type IV bone at the tissue level. In addition, nanoindentation measurements of the bone tissue harvested at femur/tibia from the same patients were compared with the results from the iliac crest biopsy. Young's modulus and hardness values were not significantly different between the two anatomic locations in either cortical or trabecular measurements. The ratio of E/H was not significantly different between the two groups. Results indicate that intrinsic modulus, hardness, and indentation deformation pattern (E/H) of OI bone tissues are not significantly different at long bone (midshaft of femur/tibia) and iliac crest. We observed that age (1.9 to 13.2 years) did not influence OI bone tissue intrinsic mechanical properties.

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“…Recent research has uncovered many abnormalities in both collagen and mineral in oim mice including altered mineral crystal size, heterogeneity and composition [6][7][8][9][10][11][12][13][14], changes in collagen content and cross-linking [6-8, 12, 13] and abnormal collagen fibril structure [15,16].…”

Section: Introductionmentioning

confidence: 99%

Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta

Bart

Hammond

Wallace

2014

Connective Tissue Research

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Osteogenesis imperfecta is a congenital disease commonly characterized by brittle bones and caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The oim model has a natural collagen mutation, converting its heterotrimeric structure (two α1 and one α2 chains) into α1 homotrimers. This mutation in collagen may impact formation of the mineral phase, creating a brittle bone phenotype in this animal. Femurs from male wild type (WT) and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanoscale that may partially contribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure obtained Multi-scale analyses of this nature offer much in assessing how molecular changes compound to create a degraded, brittle bone phenotype.

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Bone Material Elasticity in a Murine Model of Osteogenesis Imperfecta

Cited by 19 publications

References 54 publications

Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice

Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice

Comparison of Nanoindentation Measurements Between Osteogenesis Imperfecta Type III and Type IV and Between Different Anatomic Locations (Femur/Tibia versus Iliac Crest)

Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta

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